Natural killer cells (NK cells) are a component of the innate immune system. These cells are classified as cytotoxic lymphocytes. These cells are unique and different to other cells of the immune cells in that they do not require prior exposure to antigen and do not have receptors for recognition of specific antigen sequences. Rather, NK cells express activating and inhibitory receptors that recognize ligands on target cells, with activation of NK cells dependent on the balance of activating and inhibitory signals mediated by these receptors. Importantly, NK cells express killer immunoglobulin-like receptors (KIR) that are inhibited by Class I major histocompatibility (MHC) markers on target cells. Transformed or virally infected cells downregulate MHC class I molecules and are therefore susceptible to killing by NK cells. In an normally functioning immune system NK cells play a primary role in the destruction of many types of tumor cells and various human cells of infected by viruses. NK cells induce apoptosis in target cells by releasing various factors in to the target cells that activate the cells own apoptotic pathway.
Given the recalcitrance of many tumor cells to all known therapies to treat cancer and the adverse side effects associated with even many of the best therapies to treat cancer there remains a profound need for new compounds and methods to treat cancerous tumors. Some aspects of the invention seek to address these needs.